Individuals with Attention Deficit Hyperactivity Disorder (ADHD) are more likely to smoke cigarettes than the general population, start smoking at younger ages, progress to regular use and dependence more quickly, and have a harder time quitting. The specific factors that confer risk for smoking-related outcomes among those with ADHD have not been thoroughly evaluated, though a range of possibilities exist. To date, the majority of research investigating the ADHD-smoking link has been descriptive in nature and almost no experimental studies have been conducted in those with ADHD who are not already regular cigarette smokers. The purpose of this application is to evaluate the effects of acute nicotine exposure in a group of nonsmoking young adults with and without ADHD (N= 75/group). We will use a novel approach for evaluating nicotine effects by using nicotine nasal spray. This will allow for an ethically defensible and valid way of modeling the initial effects of cigarette smoking in a group of individuals at risk for smoking. We will first assess the subjective, physiological, and performance effects of several different doses of intranasal nicotine. We will then assess the reinforcing effects of nicotine under conditions of high versus low cognitive demands. Finally, we will examine the moderating effects of several gene variants on the outcomes. In general, we hypothesize that the pattern of effects of initial nicotine exposure in those with ADHD will be different from non-ADHD individuals and that the effects will be related to genetic variation. These differences will help explain the increased risk for smoking in individuals with ADHD and will have implications for prevention and treatment of smoking in this clinical population as well as, potentially, for the general population. PUBLIC HEALTH RELEVANCE: Individual with Attention Deficit Hyperactivity Disorder (ADHD) is more likely to smoke cigarettes than the general population. They are also more likely to become regular smokers more quickly following initial use. Little is known about why individuals with ADHD are at increased risk for smoking. This research will identify factors associated with initial nicotine exposure that may help to explain why individuals with ADHD smoke more often.